Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

Abstract

Heart failure after myocardial infarction (MI) is the leading cause of death worldwide. Citri Reticulatae Pericarpium (CRP) is a traditional Chinese herbal medicine that has been used in the clinic for centuries.In this study, we aimed to investigate the roles of CRP in cardiac remodeling and heart failure after MI, as well as the molecular mechanisms involved. MethodsMale C57BL/6 mice aged 8 weeks were subjected to coronary artery ligation to mimic the clinical situation in vivo. Echocardiography was used to assess the systolic function of the mouse heart. Masson trichrome staining and Wheat germ agglutinin (WGA) staining were utilized to determine the brotic area and cross-sectional area of the mouse heart, respectively. Cardiomyocytes and broblasts were isolated from neonatal rats aged 0-3 days in vitro using enzyme digestion. TUNEL staining and EdU staining were performed to evaluate apoptosis and proliferation, respectively. Gene expression changes were analyzed by qRT-PCR, and protein expression changes were assessed by Western blotting. ResultsOur ndings revealed that CRP attenuated cardiac hypertrophy, brosis and apoptosis and alleviated heart failure after MI in vivo. Furthermore, CRP mitigated cardiomyocyte apoptosis and broblast proliferation and differentiation into myo broblasts. In addition, the PPARγ inhibitor T0070907 completely abolished the abovementioned bene cial effects of CRP, and the PPARγ activator rosiglitazone failed to further ameliorate cardiac apoptosis and brosis in vitro. ConclusionCRP alleviates cardiac hypertrophy, brosis, and apoptosis and can ameliorate heart failure after MI via activation of PPARγ.

Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention

“…Moreover, zerumbone, ganxin V, nutmeg-5, ginsenoside Rg2, jatrorrhizine, cardiotonic pill, and huoxin pill all regulate the TGF-β1/smad pathway to attenuate fibrosis ( Li et al, 2020d ; Wang et al, 2021b ; Yan et al, 2022a ; Yan et al, 2022b ; Li et al, 2022c ; Hao and Jiao, 2022 ; Liang et al, 2022 ). Moreover, citri reticulatae pericarpium also reduces CMs apoptosis, CFs proliferation, and CF-to-MF transformation by upregulating PPAR-γ expression ( Chen et al, 2022c ), while auraptene improves cardiac hypertrophy and dysfunction via activating PPARα ( Sunagawa et al, 2022b ). Tanshinone IIA suppresses inflammation and fibrosis via the regulation of NADPH oxidase 4 ( Chen et al, 2021b ).…”

Mechanism of Citri Reticulatae Pericarpium as an Anticancer Agent from the Perspective of Flavonoids: A Review

“…To date, CRP has proven effects in the respiratory system, including but not limited to inhibiting airway inflammation, fighting acute lung injury and pulmonary fibrosis [ 8 , 9 , 10 , 11 , 12 , 13 ]. In terms of the cardiovascular system, CRP can improve cardiac insufficiency, alleviate cardiac hypertrophy and myocardial fibrosis, prevent hyperlipidemia and keep cardiomyocytes away from the damage of hypercholesterolemia [ 14 , 15 , 16 , 17 , 18 ]. Experiments have found that CRP’s neuroprotective properties confer the ability to prevent neurodegeneration caused by Parkinson’s, Alzheimer’s, Huntington’s disease and multiple sclerosis [ 19 , 20 , 21 , 22 ].…”